HSC70 Inhibits Spring Viremia of Carp Virus Replication by Inducing MARCH8-Mediated Lysosomal Degradation of G Protein

As a fierce pathogen, spring viremia of carp virus (SVCV) can cause high mortality in the common carp, and its glycoprotein (G protein) is a component of the viral structure on the surface of virion, which is crucial in viral life cycle. This report adopted tandem affinity purification (TAP), mass spectrometry analysis (LC-MS/MS), immunoprecipitation, and confocal microscopy assays to identify Heat shock cognate protein 70 (HSC70) as an interaction partner of SVCV G protein. It was found that HSC70 overexpression dramatically inhibited SVCV replication, whereas its loss of functions elicited opposing effects on SVCV replication. Mechanistic studies indicate that HSC70 induces lysosomal degradation of ubiquitinated-SVCV G protein. This study further demonstrates that Membrane-associated RING-CH 8 (MARCH8), an E3 ubiquitin ligase, is critical for SVCV G protein ubiquitylation and leads to its lysosomal degradation. Furthermore, the MARCH8 mediated ubiquitylation of SVCV G protein required the participation of HSC70 through forming a multicomponent complex. Taken together, these results demonstrate that HSC70 serves as a scaffold for MARCH8 and SVCV G, which leads to the ubiquitylation and degradation of SVCV G protein and thus inhibits viral replication. These findings have established a novel host defense mechanism against SVCV.

Syntax-Semantic Types and Lexico-Semantic Models of Multi-Component Words in Old Bulgarian and Church Slavonic: Composita Substantiva & Verba

The proposed article examines the syntactic-semantic types and the lexico-semantic models of multi-component complex words from the category of substantives and verbs in Old Bulgarian and Church Slavonic. The study is done on lexical material, excerpted from the main lexicography works in Old Bulgarian and Church Slavonic languages. The analysis proceeds from the theoretical statement that the structural significance of word order (as well as of any language unit that is semantically and formally dissected) is not a simple sum of lexical meanings of its constituent units, but interactions between them on the basis of certain predicate relations. Based on the specific analysis, the conclusion is drawn that the variety of syntactic-semantic types and the lexico-semantic models of multicomponent complex words reveals the rich word-forming capabilities of the Old Bulgarian language, respectively the Church-Slavic language, and their ability to adequately translate foreign language specimens by their own means of speech.

Textual characteristics of multicomponent structures built according to sequential subordination and parallel models

The object of the analysis is complex sentences including two or more subordinate clauses with the meaning of condition, cause, purpose, concession, which in general constitute the category of conditionality. Multicomponent sentences expressing the close interconnection of these relations represent a microtext, making it possible to study various textual characteristics. The analysis is based on the multicomponent complex sentences built according to models of sequential subordination and parallel models, and is devoted to their textual characteristics. The latter include both universal text categories inherent in any text, and optional, inherent only in certain types of text. It is shown how the main text categories such as cohesion, processuality, integrity, continuum are realized within the microtext-sentence. The interrelation of the structure of multicomponent complex sentences, their content and the communicative task of the statement is emphasized. On the example of contaminated structures with various types of connection (compositional, subordinate, asyndetic), it is shown that the combination of multiple methods and techniques constitutes tectonic means of text formation. It is confirmed that in the structural-semantic context, the main nominative and communicative units of the language system, a word and a sentence, acquire meaning increments and turn into “text words” and “text sentences”. It is concluded that multicomponent complex sentences with subordinate clauses are microtext with more or less integral meaning. The combination of various types of syntactic link, various types of inclusions, repetition, parallelism, providing a clear structural form of complex constructions, on the one hand, are means of dispersing meanings, and on the other hand, they unite separate structural and semantic components of the statement into a single whole, creating the basis of text-forming relations.

Text categories and text-forming potential of multicomponent collaterally subordinating constructions with the meaning of conditionality

In a series of complex study of multicomponent or polypredicative complex sentences, it is relevant to consider them as a microtext. In the text study discussion issues still exist: the number and composition of categories, the means of their expression, the difference between the concepts of “textual characteristic” and “text-forming function”. Based on the material of multicomponent complex sentences, we consider universal text categories inherent in any text, and optional, inherent only to certain types of text. The principal categories of the text, such as cohesion, coherence, integrity, consistency, continuum are realized even within the limits of a microtext-sentence. The analysis of multicomponent structures is carried out in a triune way: taking into ac-count the relation of their form, meaning and function. We show that the sequence of homogene-ous subordinate clauses is determined by their content and the communicative task of the state-ment. In this regard, as the utterance unfolds from one subordinate clause to another, either the concretization of the meaning of conditionality or its intensification is revealed. On the other hand, the connection to the subordinate clauses of constructive conjunctions and lexical actualizers contributes to the expression of the category of informativeness, which implies the reflection in the text of the degree of novelty or significance of information. On the example of contaminated structures with various types of communication (compositional, subordinate, non-union), various methods and techniques are described as tectonic means of text formation. Thus, we conclude that a multicomponent complex sentence, which is a transitional structure from a complex sentence to a text, makes it possible to study the interaction of lexical and syntactic means in the formation of the meaning and implementation of the author’s communicative intention.

Simultaneous improvement of ketoconazole solubility, antifungal and antibiofilm activity by multicomponent complexation

Background: A novel multicomponent complex (MC) of ketoconazole (KET) with β-cyclodextrin (β-CD) and N-acetylcysteine (NAC) was developed with the purpose of improving the solubility as well as the antifungal and antibiofilm activity of KET against Candida albicans. Results & methodology: The interactions among the components were studied using nuclear magnetic resonance, thermal analysis, powder x-ray diffraction, infrared spectroscopy and scanning electron microscopy. Phase-solubility studies demonstrated a considerable increase in the solubility of the MC. An enhancement in antibiofilm and antifungal activity of MC was determined against C. albicans by XTT assay and microbiological studies. Conclusion: This MC, with improvements in the drug pharmaceutical performance, might have an important potential in the development of new pharmaceutical formulations of KET.

ROLE OF ENDOGENIC INTOXICATION IN MUSCLE INJURY IN EXPERIMENT

Background. Endogenous intoxication is a multicomponent complex process due to the endogenous biological products or dysfunction of systemic natural detoxification. Objective. The aim of the research was to study the dynamics of indices of endogenous intoxication in rats with traumatic muscle damage in the experiment. Methods. The experiment was performed on 45 non-linear white rats, which were modeled with traumatic muscle damage. The level of endogenous intoxication was assessed by the content of medium plasma molecules (MMM), leukocyte and erythrocytic index of intoxication (LII and EII). The research was conducted on the 1st, 3rd, 7th, 14th days after the injury. Results. It was found that traumatic muscle damage causes endotoxemia. Manifestations of endogenous intoxication are: the increase of MMM1 in 2.3 times, MMM2 in 2.8 times compare to the intact animals. The level of this indicator slightly decreased in 7 days. Simultaneously with an increase in the MCT level in the post-traumatic period, the total toxic effect on the erythrocyte membrane also increased, which was manifested by a significant increase in EII in all terms of observation. Conclusions. Traumatic damage of the muscles is accompanied by the growth of molecules of average mass in upto 7 days of observation, which significantly differ from the indicators of the intact group. The results of our research prove that traumatic muscle damage causes endotoxicosis development evidenced by accumulation of endotoxins in the animals’ body that is proved by significant changes in endogenous intoxication indices: i.e. erythrocytic and leukocytic indexes of intoxication and content of medium mass molecules.

The aphoristic character of Taras Melnychuk’s poetry: the stylistic and syntactic aspect

The article reveals the individual stylistic features of T. Melnychuk’s poetic language as represented in their semantic and syntactic organisation and stylistic functions. The task was to study the semantics of the aphorisms, their syntactic structure and stylistic means and to identify the compositional functions. According to the degree of the semantic dominant expression, the aphorisms of the analysed poetry are figurative and concentrate around the themes and motifs that have to do with Ukraine, its history, the destiny of the poet himself, with moral and ethical issues, with eternal values. The comprehensiveness of the aphoristic character of the analised poems is proved. T. Melnychuk’s aphoristic expressions are established to correlate with various syntactic constructions: from a simple sentence to overphrase unities. The registered poetic aphorisms are mostly equivalent to complex sentences of minimum structure with adverbial clauses of condition or cause as well as attributive clauses etc. The aphorisms are also represented by multicomponent complex sentences and coordinate constructions (the latter have mainly comparative-contrastive relations between the predicative parts) and, more seldom, by asyndetic sentences. Prevalence of the aphorisms equivalent to composite sentences and overphrase unities can be explained by their being not only sense-making but also compositional components of T. Melnychuk’s poems. There are whole strophes or poems of aphoristic character. T. Melnychuk’s aphoristics is characterised by folkloristic nature, by tending to maxims. The aphoristic character is based on paradoxical features and is created by various oppositions, repetitions, negation, chiasmus, is supported by rhyming.